Abstract 6515: Pancreatic ductal adenocarcinoma (PDAC) early detection

Abstract Introduction Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and is one of the deadliest cancer in the U.S., with a 5-year survival rate of just 11%. It is expected that ~62,000 new cases will be diagnosed in the US in 2023 and >70% of those will be at the regional or distant state, when curative resection is no longer an option. It is imperative that tools enabling early disease detection (stages I and II) are developed to improve patient survival outcomes. Here, we report the results of a study on the utility of extracellular vesicles (EVs) for early PDAC detection. Methods Our case-control training set was comprised of 75 pathologically confirmed PDAC cases (Stage I = 31, Stage II = 44) and 640 controls (including 11 subjects with pancreatitis) for EV biomarker and algorithm selection via machine learning. EVs from plasma were isolated using a proprietary technology, then EV-bound proteins of interest were analyzed via an immunoassay. A second independently collected cohort of 20 confirmed PDAC cases (Stage I = 10, Stage II = 10) and 27 controls (including 9 patients newly diagnosed with diabetes) was used for validation. Results The machine learning analysis using EV-isolated proteins generated a signature that utilized 8 different biomarkers, with an AUC of 0.989 (95% CI: 0.980 - 0.998) in the training set and an AUC of 0.987 (CI: 0.964 - 1.000) in the validation set. For the validation set, the sensitivity was 95% (CI: 76.4% - 99.1%) and the specificity was 92.6% (CI: 76.6% - 97.9%), with 10 out of 10 stage I cases and 9 out of 10 stage II cases correctly classified. Conclusions The ability to alter the future outcomes of PDAC patients will be predicated on development of a new generation of early-detection biomarkers and technologies. The use of EV protein signatures, a new class of cell-free biomarker, permits detection at high sensitivity and specificity, as demonstrated for the independently collected validation cohort. Studies aimed to assess this test for high-risk patients (family history of PDAC, known germline mutations, precursor lesions, hereditary pancreatitis, new onset diabetes will continue towards the establishment of real-world evidence. Citation Format: Juan P. Hinestrosa, Harmeet Dhani, Gregor Schroeder, Jean M. Lewis, Heath I. Balcer, Razelle Kurzrock, Dove Keith, Rosalie Sears, Paul Billings. Pancreatic ductal adenocarcinoma (PDAC) early detection. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6515.